Process for producing 2-hydroxy-4-methylthiobutyric acid (MHA) and its use as feed stuff supplement

ABSTRACT

Known processes for producing 2-hydroxy-4-methylthiobutyric acid (MHA) use a liquid-liquid extraction or a combined liquid/liquid and solid/liquid phase separation to isolate MHA from a reaction mixture produced by hydrolysing MMP-cyanhydrine. These processes are either costly or produce waste that is difficult to dispose of. These disadvantages are eliminated by isolating MHA by solid/liquid separation. The reaction mixture is evaporated until a MHA-containing salt residue with little or no residual water is obtained the MHA-containing, salt residue is treated with an organic solvent to produce a suspension, solid components are separated from the thus obtained suspension until a MHA-containing solution is obtained, the organic solvent is removed from the MHA-containing solution until a MHA residue is obtained and if required the MHA residue is then conditioned by water admixture. Besides high quality MHA, this process produces marketable crystalline ammonium sulphate and/or hydrogenated ammonium sulphate. This process is useful for producing feedstuff supplements.

This application is based on German Patent Application 4428608.2 filedAug. 12, 1994 and PCT/EP98/03068 filed Aug. 2, 1995, the contents ofwhich are incorporated hereinto by reference.

This application is based on German Patent Application 4428608.2 filedAug. 12, 1994 and PCT/EP98/03068 filed Aug. 2, 1995, the contents ofwhich are incorporated hereinto by reference.

The invention is relative to a process for producing2-hydroxy-4-methylthiobutyric acid (MHA) according to the generic partof claim 1 as well as to the use of the MHA produced according to thisprocess.

In particular, the invention is relative to an improved, novel processfor simultaneously obtaining MHA and crystalline ammonium sulfate orammonium bisulfate in high yield and purity while avoiding a waste waterwhich requires treatment and optionally contains salt.

2-hydroxy-4-methylthiobutyric acid (MHA) is the hydroxy analogue of theessential amino acid methionine in racemic form and is, like the latter,an important additive in animal nutrition. In the raising of poultry MHAexhibits similar growth-stimulating properties like the amino acid knownfor this. However, the additive is also becoming increasinglyinteresting in other areas of animal nutrition.

BACKGROUND OF THE INVENTION

MHA is usually used in the form of aqueous concentrates which alsocontain a certain amount of oligomers, primarily the di- and trimericlinear ester acids, in addition to the monomer. The content of theseoligomers is a function of the production conditions and theconcentration selected. However, on account of their low nutritiveefficiency and the unfavorable influence on the flow properties due toelevation of viscosity it is desirable to keep their percentage as lowas possible. Commercial formulations have, at a total concentration of8-90% by weight, less than 20% by weight, preferably less than 17% byweight in the sum of oligomers, corresponding to a monomer/oligomerratio of ˜4:1 to 5:1.

The use of the calcium salt and of the mixed calcium ammonium salt ofMHA as feedstuff additive is also known. However, the production ofthese salts is associated with higher production costs. Moreover, theyare harder to mix in as powdery solids into the feedstuff formulationthan the aqueous concentrates of the free acid with a low amount ofoligomers, which concentrates can be readily sprayed.

The synthesis path to MHA consists of 3 reactions.

The general process for the production of MHA starts with3-methylthiopropionaldehyde, also designated asmethylmercaptopropionaldehyde or MMP, which is reacted with hydrogencyanide to 2-hydroxy-4-methylthiobutryonitrile, also designated asMMP-cyanohydrin or MMP-CH (equation I). ##STR1##

The MMP-cyanohydrin produced is subsequently customarily hydrolyzed withstrong mineral acids via the intermediate stage of2-hydroxy-4-methylthiobutyramide, also designated as MHA amide,(equation II) ##STR2## to the methionine hydroxy analog (MHA) (equationIII). ##STR3## This hydrolysis can be carried out in one or in twostages.

A two-stage procedure starting with MMP-cyanohydrin is described in U.S.Pat. No. 2,745,745; 2,938,053 and 3,170,000. In them the cyanohydrin isfirst reacted to the MHA amide at relatively low temperatures withconcentrated mineral acid, e.g. with 50-85% sulfuric acid, whereupon thehydrolysis to MHA is continued after the addition of water at elevatedtemperature. The calcium- or calcium ammonium salt of MHA and calciumsulfate as coupling product are obtained therefrom by treating thesaponification mixture with calcium hydroxide or--carbonate. In order toreduce the compulsory accumulation of worthless byproducts the twopatents cited first recommend that the hydrolysis agent sulfuric acid beadded in a hypostoichiometric ratio to the MMP-cyanohydrin, e.g.0.55-0.8:1. British patent 722,024, which describes the same type offormation of the MHA salts starting with MHA amide, implies thetwo-stage procedure.

The processes published in European patents 0,142,488 (with sulfuricacid) and 0,143,100 (with mineral acid), which have as subject matterthe obtention of MHA in liquid form, that is, highly concentratedaqueous solutions, use the two-stage hydrolysis. The latter is obtainedafter the hydrolysis reaction, carried out under defined conditions ofconcentration and temperature via the amide stage with excess mineralacid, with the aid of a solvent extraction, in which certain solventspartially miscible with water are used. Although MHA concentrates areobtained in high quality and yield according to these processes there isthe problem here of the coupling product ammonium bisulfate remaining inthe aqueous raffinate. No data is presented about its use or disposal.

Concentrated MHA solutions are obtained without the aid of a solventaccording to U.S. Pat. No. 3,773,927 by means of a two-stage hydrolysisof MMP-cyanohydrin with aqueous hydrochloric acid in an excess,subsequent concentration of the saponification mixture and separation ofthe crystallized ammonium chloride. However, the MHA concentratesobtained in this manner are rich in oligomers and colored black. Eventhe separated ammonium chloride is heavily contaminated.

According to U.S. Pat. No. 4,353,924 the excess mineral acid isneutralized with ammonia or other alkaline substances after thehydrochloric two-stage hydrolysis. This yields concentrated MHAsolutions with lesser corrosive properties. However, the ammonium saltproblem is the same. It order to eliminate this problem U.S. Pat. No.4,310,690 describes a process in which the matter is neutralized afterthe hydrolysis with hydrochloric acid under precisely defined conditionswith sodium hydroxide solution and the ammonium chloride converted intocommon salt and ammonia. In the subsequent treatment with caustic limethe MHA calcium salt is obtained as suspension in a practicallysaturated sodium chloride solution. After the solid-liquid separationthe filtrates are returned for the most part to the preparation of thecaustic-lime suspensions. In this manner the wastewater load is reducedand the co-production of ballast substances which impact the environmentis avoided. No data is presented about the use or the whereabouts of theammonia produced as secondary product.

Single-stage hydrolysis processes are also described in the patentliterature. Thus, the process according to British patent 915,193 isrelative to the obtention of MHA calcium salt, in which process afterthe saponification of MMP-cyanohydrin with dilute sulfuric acid in anexcess the MHA form is separated by extraction with higher-boilingethers from the saponification solution and MHA calcium salt obtained bysubsequent treatment of the extract with calcium hydroxide. However, thereturn of the aqueous raffinate into the saponification stage providedin this continuous process results in an accumulation of the inorganiccompanions.

Another single-stage hydrolysis process with sulfuric acid assaponification agent is published in European patent 0,330,527 whichmakes do without solvent and results directly in concentrated aqueousMHA solutions. Crystalline ammonium sulfate in marketable form isobtained thereby as co-product. This goal is achieved in that thesaponification mixture is neutralized with ammonium hydroxide solutionto the extent that the excess mineral acid and the ammonium bisulfateproduced are converted into the neutral sulfate, during which two liquidphases are produced which for their part are separated and concentratedby evaporation in order to obtain liquid MHA on the one hand andcrystalline ammonium sulfate on the other hand. The various filtrationand return steps are combined in such a manner thereby that practicallyno product is lost and no waste water loaded with salt is produced. Theresulting MHA has a quality similar to that of the product obtainedaccording to EP 0,142,488.

However, even this ecologically acceptable process has variousdisadvantages. As the applicant of the present invention determined whenreworking this process, for the one, distinctly higher acid excessesthan are indicated must be used, conditioned by the comparatively ratherhigh dilution of the sulfuric acid (20-50%) in order to achieve acomplete conversion of cyanohydrin. Also, in order to avoid saltseparations during the neutralization the work must be carried out in arather high dilution in order to be able to cleanly separate the twoliquid phases. For the other, the isolated ammonium sulfate is of asticky consistency and has an intensive odor, so that a posttreatmentsuch as e.g. a wash filtration or recrystallization appears to beunavoidable, which adds additional expense to the process. Also, theprocess uses more energy in the evaporation steps--other thanpostulated--than the process of EP-A 0,142,488 cited by way ofcomparison. Moreover, the solid treatment provided with two separatestrings with filtration/centrifugation is cost-intensive and verycomplex as concerns the apparatus involved as is the drying of theammonium sulfate (not indicated in the flow chart).

In view of the state of the art indicated herein as well as of thedisadvantages associated with the known processes, the invention has theproblem of indicating another process for producing2-hydroxy-4-methylthiobutyric acid (MHA) in accordance with theinitially mentioned kind which should be as simple and economical aspossible as regards the workup of the reaction products but at the sametime largely avoids the occurrence of undesired waste substances.

SUMMARY OF THE INVENTION

These and other problems not indicated in detail are solved with aprocess containing the features of the characterizing part of claim 1.

As a result of the fact that during the isolation of the MHA thereaction mixture is concentrated by evaporation under obtention of anMHA-containing salt residue containing a slight residual water contentto being practically free of residual water, the MHA-containing saltresidue is subsequently treated with an organic solvent under obtentionof a suspension, the solid components are subsequently separated fromthe suspension under obtention of an MHA-containing solution, theorganic solvent is thereafter removed from the MHA-containing solutionunder obtention of an MHA residue and the MHA residue is conditionedthereafter, if necessary, by the addition of water, a process is madeavailable in accordance with the invention which permits the productionof liquid MHA with excellent quality and which in particular avoids theformation of a waste water loaded with salt and the liquid MHAaccumulating along with crystalline ammonium sulfate or ammonium bisulfate is distinguished especially by a low amount of oligomers and bya high degree of purity. In particular, the liquid MHA obtainable inaccordance with the invention is essentially free of organic impurities.

Within the framework of the invention the MHA is isolated from thereaction mixture preferably by a solid/liquid separation in which anessentially solid, MHA-containing salt residue is treated with anorganic, inert solvent which is completely, partially or evennon-miscible with water.

This procedure clearly differs from the processes known from the stateof the art in which the MHA is isolated from the reaction mixture(hydrolysate) either by liquid/liquid extraction (EP 0,142,488) or bycombined liquid/liquid and solid/liquid phase separation (EP 0,330,527).Whereas the MHA isolation according to the first-named patent makes dowithout a solid treatment and according to the last-named patent theisolation of MHA from an MHA-containing hydrolysate proceeds without theuse of a solvent, the process in the isolation of the MHA from thehydrolysate according to the present invention comprises both a solidtreatment and also the use of an organic solvent for isolating the MHAbut offers, in contrast to the processes known from the state of theart, the decisive advantage that it also permits, along with theproduction of liquid MHA with advantageous properties, especially with alow amount of oligomers, the production of one of the two ammonium saltsof sulfuric acid (ammonium sulfate or ammonium hydrogen sulfate) in highpurity, that is, in marketable form.

DETAILED DESCRIPTION OF THE INVENTION

A significant advantage of the novel process resides in the fact that incontrast to the process according to EP 142,488 no waste water isproduced which contains inorganic salts and therefore requirestreatment, the disposal and/or workup of which is problematic andcost-intensive, whereas in contrast to the process of EP 330,527 thisproblem is solved with lesser expenditure of energy, lesser expense forapparatuses and, as regards the obtention of ammonium sulfate or-bisulfate as co-product, with a higher product quality which makes aposttreatment not necessary. In particular, a comparison of the processof the invention with the process known from EP 330,527 shows that theenergies to be expended in the last-named process for the variousevaporation steps are nearly twice as high, more precisely stated, 1.8times as high, not taking into account the energy still required for theposttreatment of the salt according to EP 330,527 for conversion into amarketable form.

The evaporation of the reaction mixture obtained after the hydrolysis inone step and the decomposition of the product mixture largely freed tocompletely freed of water with the aid of an inert solvent in which theMHA is soluble and the ammonium sulfate or ammonium bisulfatepractically insoluble into a liquid component containing the MHA indissolved form and into a crystalline component containing the ammoniumsalt which can be separated from one another are especially advantageousin the process of the invention.

The evaporation of the reaction mixture obtainable after the hydrolysiscan take place in any manner known to an expert in the art.

The greatest possible freedom from water of the evaporation residue isuseful in order to achieve the completest possible subsequent separationof the MHA from the MHA-containing salt residue remaining after theevaporation. On the other hand, the conditions required for evaporationare to be selected as protectively as possible so that an unnecessarydamaging of the MHA-containing residue is avoided. Slight residual watercontents are preferred, e.g. ≲5% (percent by weight) relative to thetarget product MHA. It is especially advantageous if the reactionmixture is freed essentially completely from water after the hydrolysis.The expression "freed essentially completely from water" does not denotethe absolute absence of water in this connection. Rather, a residualwater content which is customary under the conditions of vacuum andtemperature to be preferably observed is accepted which, however, canextend to a practical freedom from residual water.

It can be especially advantageous for the invention that the evaporationof the reaction mixture is carried out in a continuous manner. Acontinuous process makes possible the use of very protective conditions,especially very short residence times of the reaction mixture to befreed from the water in the unit used for the evaporation. All unitsfamiliar to an expert in the art can be considered for this, includinge.g. suitable evaporators such as e.g. a film evaporator equipped withrotor, and similar units.

The reaction mixture to be concentrated by evaporation and largely freedof water can be subjected, optionally and preferably before the drawingoff of the water, preferably in a vacuum, before and/or during theactual evaporation to an adiabatic evaporation cooling under applicationof a vacuum to approximately 60° C. or less in order to remove anyvolatile or odor-intensive components of the reaction mixture. This hasthe additional effect that these components can be held separate fromthe main amount of the water to be drawn off later.

It is furthermore advantageous if the saponification solution, that is,the reaction mixture, is treated after treatment with sulfuric acid withammonia, preferably gaseous, and is neutralized thereby either up to thecomplete formation of ammonium sulfate or only partially to the bluntingof any free sulfuric acid still present. This step can also beeliminated in the case of the striven-for byproduct ammonium bisulfate.

It can also be preferred in a large-scale realization of the process ofthe invention that the ammonium sulfate salts obtained after thesolid/liquid separation in solid form are conducted, optionally afterprevious evaporation of solvent remnants and being slurried with water,to a sulfuric acid--contact system under recovery of sulfuric acid.

It is furthermore also possible that the evaporation of the reactionmixture is carried out without previous or subsequent neutralizationwith ammonia and that the ammonium bisulfate obtained after thesolid/liquid separation in solid form is conducted, optionally afterprevious evaporation of solvent remnants and being slurried with water,to a sulfuric acid--contact system under recovery of sulfuric acid.

There is a plurality of solvents which are possibilities for thesubstance separation (take-up of the bottom product largely tocompletely freed of water and separation of the liquid from the solidphase) and which meet the conditions of chemical indifference and lowsolubility for ammonium sulfate and/or ammonium bisulfate. Suitablesolvents can be miscible with, partially miscible with water or evenwater-insoluble. The following can be taken into consideration: E.g.ethers such as isopropyl ether, tetrahydrofurane, dimethoxyethane,secondary alcohols such as 2-propanol, secondary butyl alcohol, ketonessuch as acetone, methylethylketone, methylisopropylketone,methylisobutylketone, aromatic hydrocarbons such as toluene, chlorinatedhydrocarbons such as carbon tetrachloride and others. Primary alcohols,esters and aliphatic and cycloaliphatic hydrocarbons are less suitable.Polar solvents which have comparatively low boiling points and heat ofevaporation and which can be recovered readily by distillation,optionally under rectifying or azeotrope-forming conditions, have provento be especially suitable from an engineering standpoint. Care mustmoreover be taken in the case of (partial) miscibility with water thatthe water content should not exceed 5% by weight in a possible recyclingof the solvent. Solvents preferred within the scope of the invention areacetone, methylisopropylketone, methylisobutylketone, isopropanol,tetrahydrofurane and toluene. Acetone is especially preferred. Evenmixtures of the previously cited solvents can be used in accordance withthe invention.

In the invention a suspension containing in particular saltprecipitating in a crystalline manner (ammonium sulfate or ammoniumbisulfate) develops from a gelatinous mass obtained as MHA-containingsalt residue after the condensation by evaporation by the addition of asolvent in accordance with the invention. Finally, the salt precipitatedin a crystalline manner and obtained by the addition of the solvent inthe form of a suspension is separated under obtention of anMHA-containing solution. This separation can basically be carried outaccording to all process variants known to an expert in the art for theseparation of solids out of solutions. Processes used with preferenceare filtration under the influence of gravity or also centrifugation.The ammonium salts crystallized out and separated in this manner areoptionally washed with the solvent used and then dried. Ammonium sulfateor ammonium bisulfate obtainable and treated in this manner isessentially free of organic impurities and is of sales quality with adegree of purity of ≳99%.

The MHA-containing solution obtained after the separation of the solidcomponents out of the suspension as filtrate or centrifugate (organicphase) is treated further in accordance with the invention for theisolation of the MHA contained in it. This preferably takes place byevaporating off the solvent, optionally under rectifying orazeotrope-forming conditions, during which it is furthermore preferredthat the recovered solvent contains no or at the most up to 5% by weightwater. It is again preferred in this connection, in order to avoid anypossible damage to the MHA, to keep its thermal loading as low aspossible by applying a vacuum.

The MHA obtainable after the evaporating off of the solvent out of theMHA-containing solution is already of a high quality and capable ofbeing sold. However, water can be optionally added for conditioning tothe MHA flowing off out of the evaporation of the organic phase underprotective conditions in order to obtain liquid MHA in a desiredconcentration of approximately 85-90% by weight (including oligomers).

Furthermore, the process of the invention should be designed to beselectively continuous or intermittent as regards the carrying out ofthe process stepsevaporation--crystallization--filtration/centrifugation--solventrecovery and final dilution of the liquid MHA. The continuous orintermittent operation makes possible an especially protective thermalproduct treatment with total residence times of the MHA from the end ofthe hydrolysis to an optional dilution with water of less than 60minutes, preferably of less than 30 minutes. Furthermore, this type ofisolation assures in an especially advantageous manner the obtention ofan approximately 85-95% by weight liquid MHA product with extremelylittle discoloration, good flow property, good thermal stability andwith comparatively low amount of oligomers of at the most 17% by weight,preferably less than 15% by weight relative to the final product.

In a further aspect the process of the invention also improves, inaddition to the isolation of the MHA from the reaction mixture obtainedby hydrolysis with sulfuric acid, the hydrolysis of the MMP-CH itself.Thus, in a process variant preferred in accordance with the inventionthe hydrolysis of the MMP cyanohydrin is carried out in two stages withthe MHA amide being obtained in a first stage and the MHA in a secondstage. The hydrolysis of MHA amide is preferably carried out in a firststage with 60-85%, preferably 65-75% sulfuric acid in a molar ratio of1:0.5 to 1:1.0, preferably 1:0.55 to 1:95 at temperatures between 20°and 60° C., preferably 30°-50° C. The MHA amide is produced therebyessentially from the MMP cyanohydrin and the mixture being produced isfurthermore essentially and advantageously practically free ofnon-converted cyanohydrin.

Furthermore, it is preferred in accordance with the invention that thehydrolysis of the MHA amide obtained in the first stage is carried outin a second stage by the addition of water and at the very least furthersulfuric acid up to the stoichiometric upper limit at temperatures of90°-110° C. preferably under reflux conditions in order to complete thehydrolysis of the MHA amide to MHA. The two-stage hydrolysis of the MMPcyanohydrin is to be carried out within the scope of the invention withsulfuric acid which is more highly concentrated in comparison to thestate of the art in a hypostoichiometric to at the most stoichiometricratio. In the case of hypostoichiometric dosing in the first hydrolysisstage (amide formation) more sulfuric acid can be supplied at a lowertemperature in order to shorten the reaction time in the second stage ,optionally until reaching the upper stoichiometric limit at elevatedtemperature in order to complete the conversion of the amide to theacid.

On the whole, the process of the invention together with the citedpreferred embodiments of the process makes possible a savings of rawmaterials, that is, of sulfuric acid by using hypostoichiometric to atthe most equal equivalents; at the same time crystalline, marketableammonium bisulfate or ammonium sulfate can be obtained along with theliquid MHA striven for as final product without formation of a wastewater loaded with salts at relatively low expenses for energy and totalconversion.

BRIEF DESCRIPTION OF THE DRAWINGS

Further aspects of the present invention result from the examplesdescribed in the following in which reference is made to the attachedfigures.

FIG. 1 shows a schematic survey for a first industrial variant of theprocess of the invention for producing MHA.

FIG. 2 shows a schematic survey for a second industrial variant of theprocess of the invention for producing MHA.

FIG. 3 shows a schematic survey for a third industrial variant of theprocess of the invention for producing MHA.

FIG. 4 shows a block diagram with the process steps of a preferredprocess variant of the invention.

EXAMPLES Example 1 Production of 2-hydroxy-4-methylthiobutyronitrile(MMP-CH)

513.8 g 99.0% 3-methylthiopropionaldehyde (4.883 moles) were placed in acoolable reaction container provided with pH electrode. The pH wasraised with triethylamine from 6.2 to 7.5. Then 135.1 g 99.0% hydrogencyanide (4.993 moles) were introduced at 30° C.±2° C. under intensiveagitation and cooling within 30-45 minutes during which the pH of thereaction solution was held constant at 7.5 by the further addition oftriethylamine. At the end of the inflow of hydrogen cyanide a total of1.08 g triethylamine had been consumed. The cooling was then removed andthe solution agitated a further 30 minutes at 30° C. After having cooleddown to ambient temperature 649.6 g of a 98.6% solution of2-hydroxy-4-methylthiobutyronitrile were obtained which was stabilizedby the addition of 85% phosphoric acid at a pH of 2.6. Analysis yieldeda conversion yield of 99.96% relative to 3-methylthiopropionaldehydeadded.

Example 2

150.2 g 65.3% sulfuric acid (1.0 mole) were placed in a reactioncontainer equipped with intensive agitator at 50° C. Within 30 minutes133.1 g 98.6% MMP-CH (1.0 mole) were added at this temperature underintensive agitation and cooling. The mixture was allowed to react afurther 30 minutes at unchanged reaction temperature whereupon thecomplete conversion of the cyanohydrin to2-hydroxy-4-methylthiobutyramide (MHA amide) was determined by HPLCanalysis. The reactor contents were then diluted with 95 g water, heatedto 90° C. and agitated for 150 minutes at this temperature. After thecompletion of the hydrolysis of the amide stage to the free acid MHA hadbeen ascertained by HPLC analysis a vacuum was applied and thetemperature of the reaction mixture lowered to approximately 70° C.under evaporation cooling. Approximately 8 g of volatile components werestripped thereby. The dealcoholized solution was treated for theconversion of the acidic ammonium sulfate formed in the reaction intoneutral ammonium sulfate with 1 mole gaseous or concentratedly sic!aqueous ammonia. Then, the water was completely evaporated off asquickly as possible in a rotating flash evaporator under a vacuum andthe remaining bottom product taken up with 200 g acetone. The MHA wentinto solution thereby whereas the insoluble ammonium sulfate settled incrystalline form. The salt was filtered off, rewashed with 25 g acetoneand dried. 130 g 99.95% ammonium sulfate were obtained. The combinedacetonic filtrates were freed of solvent in a rotating flash evaporatorand the resulting bottom product diluted with approximately 20 g waterso that an approximately 88% MHA solution was obtained. The yield of MHAincluding oligomers was 98.5% relative to MMP-CH added. The product hada yellowish color. It has a content of 11.0% of dimeric and less than 2%of trimeric constituents.

Examples 3-8

The process described in example 2 was followed; however, instead ofacetone the following solvents were used in succession for thesalt--product separation: Isopropanol, methyl-t-butylether,tetrahydrofurane, ethyl acetate, toluene, methylethylketone andmethylisobutylketone. Practically identical results for MHA and ammoniumsulfate were obtained. The amount of dimers fluctuated betweenapproximately 10 to approximately 13%, the amount of trimers was belowapproximately 2%. When tetrahydrofurane was used as separating agent thematter was repeatedly rewashed on account of the poorer filterability.

Example 9

1 mole 98.6% MMP-CH was converted to MHA as described in example 2 with1 mole sulfuric acid. After the reaction was completed the hydrolysatewas evaporated without preceding neutralization with ammonia under avacuum until constancy of weight. The practically anhydrous bottomproduct was treated with 200 g acetone. The resulting suspension wascentrifuged, the filter cake washed with 25 g acetone and dried.Filtrate mother liquor and wash solution were combined and distilledfree of solvent under a vacuum. 148.7 g of an oily residue wereobtained, corresponding to a total yield of 99% MHA which yielded afterdilution with water an approximately 88% MHA solution colored yellowwith good flow properties and good thermal resistance. The dimer contentwas determined at 15.1% whereas the trimer content was below 1.5%. Inaddition, 113 g crystalline, practically pure ammonium bisulfate wereobtained in flowable form.

Example 10

80 g 98% sulfuric acid (0.8 mole) were diluted with 40 g water (65.3%)in an apparatus with intensive agitator and reflux condenser and heatedto 50° C. 133.1 g 98.6% MMP-CH (1.0 mole) were allowed to flow in underthorough mixing and agitation within a period of 30 minutes. Afteranother 30 minutes at 50° C. an HPLC analysis indicated the completeconversion of the MMP-CH to the intermediate hydrolysis product. Theviscous mixture was diluted with 75 g water (40.2%) and heated to100°-102° C. After 3.5 hours of boiling under reflux conditions thereaction was completed and no more MHA amide was able to bedemonstrated. The brownish-colored solution was cooled down byevaporation cooling to 65° C. Approximately 15 g volatile constituentswere removed thereby. Then 13.7 g ammonia gas (0.8 mole) were bubbled infor neutralization, whereafter the mixture was evaporated in a flashevaporator until constancy of weight. 260 g of a viscous, gel-likereaction mass remained which was taken up in 200 g acetone. Theresulting suspension was filtered, the filter residue digested twicewith 25 g acetone per time and dried. 106 g 99.7% pure white ammoniumsulfate were obtained. The combined filtrates were evaporated to drynesson a rotary evaporator. 151 g oily MHA concentrate were obtained whichwas diluted with water to a content of about 88%. The dimer content inthe concentrate was 13.8% and the trimer content was below 1.5%. Thesolution has a brown color.

Example 11

Example 10 was modified in such a fashion that 1 mole MMP-CH was broughtto reaction with 0.9 mole sulfuric acid in the same concentration ratio(1st stage 65.3% aqueous, 2nd stage 40.2% aqueous) but with the furthermeasures that the intermediate hydrolysis product was boiled 3 hoursunder reflux (100°-102° C.) and 0.90 mole ammonia was used for theneutralization. After the product decomposition with acetone andsubsequent workup as described, 150 g MHA with a dimer content of 16.2%(99.9% total yield) were obtained which yielded a brownish-coloredsolution after dilution to 88%. In addition, 119 g pure white ammoniumsulfate were obtained.

Example 12

Example 2 was repeated; however, the hydrolysis time in the 2nd stagewas shortened to 1.75 hours whereas the reaction temperature was raisedto 100°-102° C. After the product decomposition with acetone and workup151 g MHA concentrate with 11.0% dimer content and less than 2% trimercontent were obtained which yielded after dilution to 88% abrown-colored solution with satisfactory flowability and thermalstability. In addition, 129 g pure white ammonium sulfate with a contentof 99.7% were isolated.

Example 13

Example 2 was repeated; however, 1.15 moles ammonia gas were used forneutralization and the time of vacuum evaporation and of acetonedealcoholization limited to 15 minutes. The yields of MHA and ammoniumsulfate were quantitative. The MHA concentrate was 98.0% with a dimercontent of 8.7% and still contained 2.0% ammonium sulfate. No moretrimers were able to be demonstrated. The yellow-colored solutiondiluted to 88% active substance content displayed excellent flowabilityand thermal stability.

Example 14

3 moles MMP-CH corresponding to a molar ratio of 0.55:1 were added to216 g 75% sulfuric acid in the course of 30 minutes at 50° C. After 30minutes of reaction time the cyanohydrin was completely converted to theintermediate hydrolysis product consisting essentially of MHA amidealong with little MHA. The mixture was then diluted with 240 g water toa sulfuric acid content of 35.5% without organic components and dividedinto 3 equal parts.

Part (1) was heated to 104° C. and agitated 4.5 h under reflux boiling,during which 35 ml water and more volatile components were distilled offafter 2.5 h. After the reaction was completed the workup described inexample 9 was followed.

Part (2) was compounded with 20 g 98% sulfuric acid, whereafter themolar ratio was 0.75:1 and the sulfuric acid concentration raised to42.8%--basis organically free. The mixture was then heated to 106° C.and held 2 h under reflux. After the reaction was completed the workupdescribed in example 9 was followed.

Part (3) was compounded with 40 g 98% sulfuric acid, whereafter themolar ratio of acid to MMP-CH and MHA amide was 0.95:1 and the sulfuricacid concentration raised to 48.5%--basis organically free. The mixturewas then held under reflux at 108°-109° C. for 1 hour. The workupdescribed in example 9 was then followed. The results can be gatheredfrom the following table.

                  TABLE                                                           ______________________________________                                             Tot.    MHA            MHA          Ammonium                             No.  yield % mon. %  Dimers %                                                                             amide Color  salt*                                ______________________________________                                        14-1 94.0    91.9     4.3   2.9   dark   57.6                                                                   brown                                       14-2 96.1    84.7    14.2   1.1   brown  80.2                                 14-3 97.6    81.3    16.3   0.1   yellowish                                                                            107.2                                                                  brown                                       ______________________________________                                         *The isolated ammonium salt is a mixture of acidic with neutral ammonium      sulfate with an amount of the former which increases in the direction 141     to 143 in correspondence with the molar ratio.                           

Example 15

1 mole MMP-CH was placed in a reaction container. 89 g 75% sulfuric acid(0.68 mole) was charged between 25°-30° C. in the course of 60 minutesunder thorough mixing and cooling. After a further 60 minutes ofagitation at 50° C. the cyanohydrin was completely converted and couldno longer be demonstrated analytically. The intermediate hydrolysisproduct was diluted with 180 g water, heated until reflux boiling andhydrolyzed 3 hours at 108° C. The reacted solution was completelyevaporated on a rotary evaporator in a vacuum and the remaining residuedigested with 200 g acetone. After filtration of the suspensionobtained, washing out of the filter residue with 2 times 25 g acetone,evaporation of the filtrate, 150 g MHA final product was obtained with adimer content of 6.5% which was diluted with water to an 87%brown-colored solution. At the same time 77 g of a pure white saltmixture of ammonium bisulfate+ammonium sulfate (98.3%) was obtainedafter the drying.

Example 16

A hydrolysis solution was produced and dealcoholized as described inexample 2. After the addition of 68 g 25% ammonia 443 g of a productmixture were obtained which had the following composition: 33.5% MHAwith 7.5% dimers, 29.3% ammonium sulfate and 37.1% water. This mixturewas evaporated to low bulk at 90° C. under a vacuum until a weight ofapproximately 300 g, whereafter the dimer content had risen onlyinsignificantly to 7.6%. The mixture was then digested with 290 gmethylisobutylketone (MIBK) and the residual water (˜21 g) distilled offazeotropically at 88° C. The resulting suspension was worked up furtherin analogy with example 2. 148.7 g MHA with a content of 8.9% dimers andless than 1% trimers as well as 131 g pure white ammonium sulfate wereobtained. After dilution of the MHA to a concentration of 88% a paleyellow solution was obtained with excellent flowability and good thermalstability.

Example 17

10 moles MMP-CH were reacted in an agitating apparatus with the samenumber of moles of sulfuric acid in accordance with the processdescribed in example 2. The raw hydrolyzate was dealcoholized underremoval of 80 g volatile components by vacuum evaporative cooling toapproximately 65° C. and subsequently neutralized with 10 moles 25%ammonia. The resulting solution was now charged continuously into aheated Sambay evaporator standing under a vacuum to which a condensatecooler and distillate receiver were connected at the top side and twocooled receiver changers provided with agitators were connected at therunoff side. The dewatering took place at 90° C./80 mbar, during whichthe product charging was regulated in such a manner that the concentraterunning off had only a minimal residual water content of less than 1%which was continuously regulated by means of Karl-Fischer titration. Thebottom product was alternatingly let into the receiver changers loadedwith aliquot amounts of acetone until the same filling height in eachone and the suspensions produced still remained capable of beingagitated. The individual fractions were separated after the stressrelief in a laboratory skimmer centrifuge, the centrifugatessubsequently washed with a little acetone and dried after the union. Thecentrifuge filtrates running off into a collecting tank were fedcontinuously into a falling-film evaporator equipped with receiverchangers and condensation devices and dealcoholized free of solventunder a vacuum. The concentrate running off was alternatingly taken upinto the bottom receivers loaded with proportionate amounts of waterunder agitation and cooling and enriched up to a content of about 88%final product. The individual fractions were united in a storagecontainer and homogenized in conclusion. After the end of the productworkup 98.8% MHA was obtained containing 11.5% dimers, 1.8% trimers and0.4% ammonium sulfate as 88% yellow solution. The yield of crystallineammonium sulfate was 95.5%.

The production of MHA and ammonium sulfate and bisulfate described inthe present example is shown in schematic fashion in FIG. 1 as anindustrial process with the main apparatuses.

The industrial device schematically shown in FIG. 1 with the mainapparatuses is operated as follows in a process in accordance with themethod of operation described in examples 2 and 17 with batchwiseproduction and continuous workup of the target products:

An approximately 65% sulfuric acid is prepared and placed in a firstagitator reactor 1, whereupon the conversion to MHA amide takes place bythe addition of the MMP cyanohydrin in the same stoichiometric ratio oralso with a slight deficit of mineral acid at approximately 50° C. whilethe reaction heat is removed via an external cooling circuit. After thecyanohydrin has been completely converted within a postreaction time themixture is discharged into a second agitator reactor 2, whereupon thehydrolysis of the MHA amide to the acid MHA is essentially concludedafter dilution to an approximately 40% concentration of sulfuric acidunder elevation of temperature at approximately 95° C. The mixture isthen transferred into a third agitator container 3 which functions bothas a postreactor as well as a buffer. From there the mixture iscontinuously fed into a container combination standing under a vacuumand consisting of separator 4a and expansion tank 4 during which themixture is cooled down to approximately 70° C. while at the same timevolatile impurities and a proportionate amount of water are drawn offwhich are fed in gaseous form or condensed to an incinerator. After thestress relief the dealcoholized mixture passes into a further agitatorcontainer 5 in which a concentrate is obtained in continuous fashion bythe pH-controlled addition of ammonia until the complete neutralizationof the sulfate ions under formation of ammonium sulfate, whichconcentrate is fed into film evaporator 6 standing under a vacuum andequipped with a rotor with condensation system 6a and 8. Atapproximately 90° C. the concentrate is dewatered in a vacuum underflash vaporization to the extent that the bottom product discharged inthe form of a gel contains only slight residual water contents ofapproximately ≳5% relative to MHA+oligomers. The bottom product is nowlet off alternatingly under stress relief in receiver changers 7a and 7bloaded with the solvent, e.g. acetone, at which time the ammoniumsulfate crystallizes out while the MHA goes into solution. The ratio ofproduct to solvent is selected so that suspensions which are stillcapable of being agitated are produced. In the case of acetone a ratioof 1:1.5-2.0 is sufficient. The aliquot suspension fractions aresupplied intermittently to skimmer centrifuge 9 and subsequently washedboth separately and with the solvent.

The resulting filter cake fractions are united and optionally suppliedto an evaporating posttreatment (not sketched into the schema) for thepurpose of recovering any still-adhering solvent remnants. The filtraterunning off into collecting tank 10 and consisting of mother liquor andwash solution is fed continuously into a film evaporator or falling-filmevaporator standing under a vacuum and provided with the appropriateperipheral equipment and completely freed of solvent at 80°-90° C. underflash vaporization--optionally under rectifying conditions in order toprevent an accumulation of water. The drawn-off solvent is suppliedafter liquefaction in condenser 11a to collecting tank 13 and returnedafter appropriate replacement of loss into the circuit process. Thebottom product which is discharged under stress relief out of theevaporator and is almost to completely anhydrous is taken upalternatingly under cooling in the two agitator receivers 12a and 12bloaded with proportionate amounts of water, enriched up to a finalproduct content of about 88-90% and then transferred to storage. Theaqueous vapor condensate evaporated off in the dewatering stage,liquified in condenser 8 and caught in collecting tank 8 can be used fordiluting the sulfuric acid in the first and also in the second reactionstage of the process, which reduces the waste water to insignificantresidual amounts stemming from the gas washers.

Example 18

Further hydrolysis batches were produced from 10 moles MMP-CH each inaccordance with the general process of example 2 and dealcoholized byevaporation cooling to 65° C. However, the obtention of the finalproduct took place differently from the method with methylisobutylketone(MIBK) described in example 17 for product separation using the processschema illustrated in FIG. 2:

The batches neutralized in agitator container 1 with 25% ammoniasolution and heated thereby to approximately 70° C. (weight: 4350-4550g, composition: 32-34% MHA, 29-30.5% ammonium sulfate, remainder water)were charged continuously into a first film evaporator 2 andconcentrated by flash vaporization at 90° C./80 mbar during whichapproximately 80-90% of the total water present was expelled and trappedvia condenser 3 in receiver 4. The concentrates still containingresidual water were alternatingly taken up in receivers 5a, 5b loadedwith MIBK in a weight ratio of 1:2 under agitation and cooling. Theresulting suspension fractions were fed continuously to a second filmevaporator (Sambay) 5 and azeotropically dewatered at 70°-75° C. in avacuum. The gel-like product mixture running off was thoroughly agitatedin cooled receiver 6 in MIBK under constant supplementation of theevaporation losses. The resulting suspension was discharged in portionswith the aid of a suitable transport member and placed on skimmercentrifuge 9. The crystal fractions centrifuged off and washed with MIBKwere collected in a storage drum for later drying. The filtrates unitedin filtrate container 10 were continuously fed into falling-filmevaporator 11 and distilled free of solvent in a vacuum. The bottomproduct running off was alternatingly taken up in receivers 12a, 12b anddiluted with water to a concentration of about 88%. The conditionedfractions were brought together in a storage container and balanced. Theyields of MHA and ammonium sulfate were about 99% with a dimer contentof the MHA of below 10%. The MHA solution had a pale yellow color, goodflowability and thermal stability. The MIBK separated during theazeotropic dewatering in phase separation vessel 8 was united with themain current recovered via vapor condensation 13, 14 and returned into anew workup cycle but now as MIBK saturated with water (˜2% H₂ O).

The aqueous phases accumulated in phase separation vessel 8 weredistilled in strip column 15 under a vacuum to remove residual MIBK. TheMIBK again distilling over azeotropically was returned into condensationsystem 7 and 8 of film evaporator 5 communicating with column 15.

FIG. 3 shows a simplified industrial performance of the process of theinvention with any desired solvent. The significance of the referencenumerals used corresponds to the reference numerals used in FIGS. 1 and2.

Example 19

The procedure of example 18 was followed; however, the followingsolvents were used in succession for product separation: 1st,methylisopropylketone, 2nd, ethyl-n-amylketone, 3d, acetic acidisobutylazetate. Yields and product properties do not differsignificantly from the preceding example.

Example 20

The procedure of example 18 was followed; however, methyl-t-butyletherwas used to separate the salt/MHA mixture and the solvent distillationsin evaporation stages 5, 11, 15 of FIG. 2 were carried out under normalpressure. The results were comparable to those of example 18.

Example 21

150 l demineralized water were placed in an enamelled, double-jacketedagitator reactor with reflux condenser and waste-gas washer withconnected vacuum pump and 300 kg 98% sulfuric acid (3.0 Kmoles) mixedin. 408 kg 96.5% MMP-CH were then added under intensive mixing in such amanner that after the reaction temperature of 50°-55° C. had beenreached the reaction heat was able to be removed via the double jacketloaded with refrigerating brine. After the infeed was over the mixturewas allowed to react 30 minutes longer and controlled for the completeconversion of the cyanohydrin. The intermediate hydrolysis productmixture consisting essentially of the acid amide MHA amide was dilutedwith 360 l demineralized water, heated to 90° C. and agitated 3 h atthis temperature. The hydrolysis was complete thereafter and MHA amidecould no longer be demonstrated. After the cooling had been removed avacuum was applied and the temperature lowered in the course ofapproximately 30 minutes by evaporation cooling to approximately 65° C.while at the same time slight amounts of volatile organic matter alongwith proportionate amounts of water, together approximately 36 kg, werestripped off and absorbed in the waste-gas washer.

The absorption liquid was detoxified with hydrogen peroxide at pH 9 aswell as deodorized and subsequently transferred to the waste-water net.After dealcoholization 1172 kg (960 1) hydrolysis solution were obtainedwith the composition of 37.9% MHA (with oligomers), 29.4% ammoniumbisulfate and 32.5% water. The solution was pumped into a measuringreceiver tempered to 65° C. and continuously drawn out of the latter bysuction into a vapor-heated film evaporator which was provided with afixed-blade rotor, had a heating area of 1.0 m² and was connected via avapor condenser together with a receiver to a vacuum system. Thesolution was dewatered with the greatest possible throughput rate at 90°C./80 mbar until less than 0.5% water in the bottom product. Theconcentrate running off was pumped under stress relief by a lobe pumpinto an agitator receiver half-filled and cooled with acetone, duringwhich the salt separated in crystalline form. After appropriate solidenrichment the suspension formed was put in portions on a link-suspendedcentrifuge while at the same time the discharged amount of acetone wasre-supplemented in the level-regulated agitator receiver. The filtraterunning from the centrifuge into a collecting tank was fed continuouslyinto a falling-film evaporator heated by warm water and with 0.5 m²heating area which had available the same supplementary units as thefilm evaporator and distilled out free of solvent at 80° C./160 mbar.The concentrate running off was pumped off under stress relief with alobe pump into a cooled agitator receiver in which the amount of waterfor adjusting a final concentration of 88% MHA, calculated for theentire batch, had already been placed. After the last loading andcentrifugation of a centrifuge filling the filter cake was repeatedlywashed out with acetone, centrifuged and collected in storage drums forsubsequent drying. The acetone with less than 0.2% water recovered inthe brine-cooled condensers of the distillation as well as of the saltdrying carried out in a blade drier was able to re reused withoutrectification after replacement of loss.

After the end of the workup cycle 442 kg (98.1%) total MHA with 13.8%dimers, 2.6% trimers and 0.2% sulfate were obtained as brownish-yellowsolution. In addition, 342 kg (99%) ammonium bisulfate were isolated.Approximately 285-290 kg sulfuric acid (100%) can be recovered therefromby thermal splitting in a sulfuric acid contact system.

The procedure described in a semi-technical manner in example 21 standsas an example for a large-scale process with batchwise production andcontinuous workup with any desired solvent (preferably ketone) in whichthe resulting ammonium bisulfate is utilized without previousneutralization in a connected sulfuric acid contact system for therecovery of sulfuric acid and the formation of nitrogen.

We claim:
 1. A process for producing 2-hydroxy-4-methylthiobutyric acid(MHA) in which the MHA is isolated from a reaction mixture obtained bythe attachment of hydrogen cyanide (HCN) tomethylmercaptopropionaldehyde (MMP) and by hydrolysis of themethylmercaptopropionaldehyde cyanohydrin (MMP-CH) obtained thereby withsulfuric acid which comprises (a) concentrating the reaction mixture byevaporation under conditions to obtain an MHA-containing salt residuesubstantially free of residual water,(b) subsequently treating theMHA-containing salt residue with an organic solvent under conditions toform a suspension, (c) separating solid components from the suspensionunder conditions to obtain an MHA-containing solution, (d) removing theorganic solvent from the MHA-containing solution and recovering an MHAresidue and, wherein the MHA residue is conditioned thereafter, ifnecessary, by the addition of water.
 2. The process according to claim 1wherein the reaction mixture is concentrated by evaporation to aresidual water content of ≲5% relative to MHA+oligomers.
 3. The processaccording to claim 1 wherein the reaction mixture is freed of residualwater.
 4. The process according to claim 1 wherein evaporation of thereaction mixture is carried out continuously.
 5. The process accordingto claim 1 wherein the reaction mixture is subjected before and/orduring the concentration by evaporation to an adiabatic evaporationcooling under a vacuum at approximately 60° C. or less in order toremove any volatile or odor-intensive components in the reactionmixture.
 6. The process according to claim 1 wherein evaporation of thereaction mixture takes place after a previous neutralization withammonia.
 7. The process according to claim 1 wherein the MHA-containingsalt residue is obtained as bottom product from (a) and is treated withacetone, methylisopropylketone, methylisobutylketone, isopropanol,toluene or tetrahydrofurane as organic solvent in (b).
 8. The processaccording to claim 1 wherein the suspension formed in (b) is filtered,during which crystalline ammonium sulfate salts in a purity ≳99%accumulate as solid components and the MHA-containing solutionaccumulates.
 9. The process according to claim 1 wherein the solvent isseparated out of the MHA-containing solution under rectifying and/orazeotrope-forming conditions and the solvent recovered contains lessthan 5% water.
 10. The process according to claim 1 wherein thehydrolysis of the MMP-CH is carried out in two stages and MHA amide isobtained in a first stage and MHA in a second stage.
 11. The processaccording to claim 10 wherein MMP-CH is hydrolyzed in the first stagewith 60-85% sulfuric acid in a molar ratio of 1:0.5 to 1:1.0 attemperatures between 20° and 60° C.
 12. The process according to claim11 wherein the mixture obtained in the first hydrolysis stage is free ofnon-reacted cyanohydrin.
 13. The process according to claim 10 whereinthe MHA amide is hydrolyzed in the second stage with the addition ofwater and further sulfuric acid up to the stoichiometric upper limit attemperatures of 90°-110° C. or under reflux conditions.
 14. A processfor producing 2-hydroxy-4-methylthiobutyric acid (MHA) in which the MHAis isolated from a reaction mixture obtained by the attachment ofhydrogen cyanide (HCN) to methylmercaptopropionaldehyde (MMP) and byhydrolysis of methylmercaptopropionaldehyde cyanohydrin (MMP-CH)obtained thereby with sulfuric acid wherein the MHA isolated from thereaction mixture comprises a solid/liquid separation in which anessentially gelatinous or solid MHA-containing salt residue is treatedwith an organic solvent.
 15. The process according to claim 8 whereinthe ammonium sulfate salts obtained in solid form are conducted,optionally after previous evaporation of solvent remnants and beingslurried with water, to a sulfuric acid--contact system for recovery ofsulfuric acid.
 16. The process according to claim 1 or claim 8 whereinthe evaporation of the reaction mixture is carried out without previousor subsequent neutralization with ammonia, and ammonium bisulfate saltsare obtained in solid form and conducted, optionally after previousevaporation of solvent remnants and slurried with water, to a sulfuricacid--contact system for recovery of sulfuric acid.